Abstract
Objective: To examine the dose response of TNFα in an ex vivo rat model of myocardial ischemia reperfusion. Methods and Results: Seventy-two rat hearts were mounted on Langendorff apparatus and perfused with oxygenated Krebs-Henseleit solutions. Ischemia was induced by reducing the perfusate flow rate. During reperfusion, incremental doses of recombinant TNFα were infused as a part of perfusate. TNFα was blocked with monoclonal TNFα antibody. Myocardial function was measured by dP/dT and relaxation time (IVRT). Cellular injury was assessed by released myoglobin and tissue concentration of malondialdehyde activity of the heart homogenates. Baseline +dP/dT was 1645±125mmHg/sec, -dP/dT was 945±73mmHg/sec and IVRT was 65±5msec. At the conclusion of reperfusion period, lower doses of TNFα increased +dP/dT and lowered IVRT. In contrast, the higher doses of TNFα decreased +dP/dT and prolonged IVRT. Pretreating the hearts with monoclonal TNFα antibody completely abolished the effects of TNFα on myocardial contractility and relaxation comparable to ischemia controls. Conclusion: Low dose TNFα improved myocardial function and decreased resultant cellular injury while high dose TNFα decreased myocardial function and increased myocardial injury following ischemia and reperfusion.
| Original language | English |
|---|---|
| Pages (from-to) | 23-35 |
| Number of pages | 13 |
| Journal | Immunological Investigations |
| Volume | 44 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2015 |
Keywords
- Myocardial infarction
- TNF alpha
- Ventricular function
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